Insights into the Friedel–Crafts Benzoylation of <i>N</i>‑Methylpyrrole inside the Confined Space of the Self-Assembled Resorcinarene Capsule

Friedel–Crafts benzoylation of <i>N</i>-methylpyrrole <b>2</b> can run inside the confined space of the hexameric resorcinarene capsule <b>C</b>. The bridged water molecules at the corner of <b>C</b> act as H-bonding donor groups to polarize the C–Cl bond of benzoyl chlorides <b>3a</b>–<b>f</b>. Confinement effects on the regiochemistry of the FC benzoylation of <i>N</i>-methylpyrrole are observed. The nature of the <i>para</i>-substituents of <b>3a</b>–<b>f</b> and their ability to establish H-bonds with the water molecules of <b>C</b> work synergistically with the steric constrictions imposed by the capsule to drive the regiochemistry of products <b>4a</b>–<b>f</b>. QM investigations indicate that inside the cavity of <b>C</b>, the FC benzoylation of <b>2</b> has a bimolecular concerted S_N2 mechanism, appropriately, above-plane nucleophilic vinylic substitution (S_NVπ)supported by H-bonding interactions between water molecules and both the leaving Cl atom and the carbonyl group.